Calcium is one of the "second messengers" that serves by relaying chemical and electrical signals within cells. A key component in this signal transduction involves the binding of calcium to a ubiquitous intracellular receptor protein called calmodulin. Calmodulin, in turn, interacts with a number of protein targets in a calcium dependent manner thereby altering a number of complex biochemical pathways that can affect the overall behavior of cells. A number of drugs with diverse applications are known to work by binding to calmodulin and thus alter the cell's response to changes in intracellular calcium. One of the most abundant and widely expressed calmodulin binding proteins is the alpha subunit of non-erythroid spectrin.
A number of calmodulin targeted drugs have been in use for some time. For instance, U.S. Pat. No. 2,645,640, discloses Chlorpromazime and related phenothiazine derivatives which are calmodulin binding drugs widely used as tranquilizers and sedatives. In addition, U.S. Pat. No. 4,117,118 discloses Cyclosporin A which is a cyclic polypeptide used as an immunosuppressive agent. This drug is thought to work by inhibiting calmodulin mediated responses in lymphoid cells. Toxic side effects from this drug have been noted, so other compounds with similar activity may allow alternative treatments with less toxicity.
One object of the present invention is to provide polypeptide sequences and compositions thereof derived from spectrin which binds calmodulin in a calcium dependent manner.
Another object of the invention is to provide clinical, pharmacological, and industrial uses of synthetic polypeptides whose structures are derived from spectrin and are capable of binding to calmodulin.